Formulary Access and the Key Drivers for Decision-making From Institution Representatives: Why Do We Select Goserelin? Why Did We Select Leuprolide? Why Did We Select Triptorelin?

Cynthia Villarreal-Garza, MD, DSc

In Latin American countries, the onset of breast cancer is approximately 10 years earlier than in high-income countries. Moreover, the incidence rate of breast cancer in individuals aged <40 years is close to 11%, which is higher than the rates in developed regions such as the United States and the European Union. Additionally, most of these young women are diagnosed with advanced-stage disease.^1,2

Gonadotropin-releasing hormone (GnRH) agonist therapy is generally preferred over oophorectomy or ovarian irradiation for several reasons, including fewer short-term side effects (which translates to better quality of life and improved treatment adherence), reversibility, proven efficacy, and reduced burden on healthcare systems. In Latin American countries, because there are delays in scheduling surgical and radiotherapy procedures, GnRH agonist therapy represents a more readily accessible option for ovarian function suppression (OFS).³

Several factors, including patient clinicopathologic risk, dosage and administration procedure, availability, cost, guideline recommendations, and physician and patient preferences, influence the selection of a specific GnRH agonist for OFS. Although criteria for identifying higher-risk patients are not well defined, this group of patients encompasses those requiring treatment with chemotherapy due to the presence of involved lymph nodes, large tumor size, high risk of recurrence, and patients diagnosed at a younger age (≤35 years) who will benefit from OFS.⁴ The Regan Composite Risk Score can be utilized to identify high-risk patients with breast cancer; however, there are no recommendations for the selection of a specific GnRH agonist based on risk.⁵

Based on a recent survey, disease and route of administration also impact GnRH agonist selection. Patients generally prefer intramuscular injections as they are associated with less pain compared with a subcutaneous implant.⁶ Familiarity and experience with GnRH agonists used in prostate cancer may play a key role in treatment selection.⁷ In Latin American countries, where resources can be limited and out-of-pocket expenditures are high, availability and cost are significant factors in the selection process of GnRH agonists.⁸

Goserelin and triptorelin have been used in pivotal clinical trials, demonstrating the benefit of adjuvant OFS. However, although the European Society for Medical Oncology, 5th International Consensus Symposium for Breast Cancer in Young Women, and the American Society of Clinical Oncology recommend adjuvant OFS in premenopausal women with early breast cancer, they do not provide recommendations for a specific drug.^9-11 A recent survey aimed at defining physician perspectives on GnRH agonist selection revealed that age is an important criterion that drives the use of GnRH agonists in patients with early breast cancer. The majority of respondents in the public sector (61.1%) chose goserelin, followed by leuprolide (33.3%) and triptorelin (5.6%). In the private sector, 42.5% of responders chose goserelin, followed by triptorelin (35%) and leuprolide (22.5%). The primary reason for choosing goserelin and leuprolide was availability.⁶ However, in a scenario of complete availability, goserelin was still the top choice, followed by triptorelin and leuprolide.

References

1. Villarreal-Garza C, Lopez-Martinez EA, Muñoz-Lozano JF, Unger-Saldaña K. Locally advanced breast cancer in young women in Latin America. Ecancermedicalscience. 2019;13:894.
2. Villarreal-Garza C, Aguila C, Magallanes-Hoyos MC, et al. Breast cancer in young women in Latin America: an unmet, growing burden. Oncologist. 2013;18:1298-1306.
3. Villarreal-Garza C, Mesa-Chavez F, Ferrigno AS, et al. Adjuvant endocrine therapy for premenopausal women with breast cancer: patient adherence and physician prescribing practices in Mexico. Breast. 2021;59:8-15.
4. Lambertini M, Del Mastro L, Viglietti G, et al. Ovarian function suppression in premenopausal women with early-stage breast cancer. Curr Treat Options Oncol. 2017;18:4.
5. Regan MM, Francis PA, Pagani O, et al. Absolute benefit of adjuvant endocrine therapies for premenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: TEXT and SOFT trials. J Clin Oncol. 2016;34:2221-2231.
6. Villarreal-Garza C. Formulary access and the key drivers for decision-making from institution representatives. Presented at Ovarian Function Suppression Summit. San Antonio, Texas. December 4, 2023.
7. Meani D, Solarić M, Visapää H, et al. Practical differences between luteinizing hormone-releasing hormone agonists in prostate cancer: perspectives across the spectrum of care. Ther Adv Urol. 2018;10:51-63.
8. Global Health Expenditure Database. Accessed December 15, 2023. https://apps.who.int/nha/database/Select/Indicators/en
9. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. J Clin Oncol. 2016;34:1689-1701.
10. Paluch-Shimon S, Cardoso F, Partridge AH, et al. ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5). Ann Oncol. 2022;33(11):1097-1118. doi: 10.1016/j.annonc.2022.07.007
11. Loibl S, André F, Bachelot T, et el. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023:S0923-7534(23)05104-9. doi: 10.1016/j.annonc.2023.11.016